Covid-19, the thyroid and the pituitary-The real state of play

Thyroid and pituitary disorders linked to the coronavirus SARS-CoV-2, responsible for the COVID-19 epidemic, are mainly due to direct infection of the endocrine glands by the virus and to cell damage induced by the immune response. The two most frequent thyroid complications of COVID-19 are low T3 syndrome, or ???non-thyroidal illness syndrome??? (NTIS), and thyroiditis. Studies among in-patients with COVID-19 have shown that between one out of six and half of them have a low TSH level, related to NTIS and thyroiditis, respectively, sometimes found in the same patient. In NTIS, the decrease in free T3 con-centration correlates with the severity of the infection and with a poor prognosis. Assessment of thyroid function in patients after a COVID-19 infection, shows normalization of thyroid function tests. Thyroiditis linked to COVID-19 can be divided into two groups, which probably differ in their pathophysiology. One is ???destructive??? thyroiditis occurring early in infection with SARS-CoV-2, with a severe form of COVID-19, usually observed in men. It is often asymptomatic and associated with lymphopenia. The other is subacute thyroiditis occurring, on average, one month after the COVID-19 episode, usually in clinically symptomatic women and associated with moderate hyperleukocytosis. Post-infection, one quarter to one third of patients remain hypothyroid. An Italian study demonstrated that low TSH in patients hospitalized for COVID-19 was associated with prolonged hospitalization and a higher mortality risk. Pituitary dis-eases associated with SARS-CoV-2 infection are much rarer and the causal relationship more difficult to ascertain. Several cases of pituitary apoplexy and diabetes insipidus during COVID-19 infection have been reported. Hyponatremia occurs in 20???50% of patients admitted to hospital for COVID-19. The prevalence of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) amongst these hyponatremic cases is difficult to determine. These endocrine complications may influence the prognosis of infection with SARS-CoV-2. Although they rarely require specific treatment, it is important that endocrinologists recognize them to ensure appropriate management, particularly in the acute phase. ?? 2022 Elsevier Masson SAS. All rights reserved.

Gene signature and immune cell profiling by high-dimensional, single-cell analysis in COVID-19 patients, presenting Low T3 syndrome and coexistent hematological malignancies.

BACKGROUND: Low T3 syndrome is frequent in patients admitted to intensive care units for critical illness and pneumonia. It has been reported also in patients with COVID-19, Hodgkin disease and chronic lymphocytic leukemia. We analyzed the clinical relevance of Low T3 syndrome in COVID-19 patients and, in particular, in those with associated hematological malignancies. METHODS: Sixty-two consecutive patients, hospitalized during the first wave of SARS-CoV-2 outbreak in Sant'Andrea University Hospital in Rome, were subdivided in 38 patients (Group A), showing low levels of FT3, and in 24 patients (Group B), with normal FT3 serum values. During the acute phase of the disease, we measured serum, radiologic and clinical disease severity markers and scores, in search of possible correlations with FT3 serum values. In addition, in 6 COVID-19 patients, 4 with Low T3 syndrome, including 2 with a hematological malignancy, and 2 with normal FT3 values, we performed, high-dimensional single-cell analysis by mass cytometry, multiplex cytokine assay and gene expression profiling in peripheral blood mononuclear cells (PBMC). RESULTS: Low FT3 serum values were correlated with increased Absolute Neutrophil Count, NLR and dNLR ratios and with reduced total count of CD3+, CD4+ and CD8+ T cells. Low FT3 values correlated also with increased levels of inflammation, tissue damage and coagulation serum markers as well as with SOFA, LIPI and TSS scores. The CyTOF analysis demonstrated reduction of the effector memory and terminal effector subtypes of the CD4+ T lymphocytes. Multiplex cytokine assay indicates that mainly IL-6, IP-10 and MCAF changes are associated with FT3 serum levels, particularly in patients with coexistent hematological malignancies. Gene expression analysis using Nanostring identified four genes differently expressed involved in host immune response, namely CD38, CD79B, IFIT3 and NLRP3. CONCLUSIONS: Our study demonstrates that low FT3 serum levels are associated with severe COVID-19. Our multi-omics approach suggests that T3 is involved in the immune response in COVID-19 and coexistent hematological malignancy and new possible T3 target genes in these patients have been identified.